Studies on the mechanism of the effects of 1,25-(OH)2vitamin D3 on bone resorption are a major current thrust of this project. a) The role of calcium in this mechanism will be tested by the use of several calcium antagonists (verapamil, ruthenium red, CoCl2) as well as divalent cation ionophores (A23187. DECYL-2). The effects of these substances to enhance or inhibit the effects of 1,25-(OH)2D3 will be examined over a range of calcium concentrations. b) The interactions between 1,25-(OH)2D3 and PTH, 25-OH-D3 and PTH and prostaglandins and PTH or 1,25-(OH)2D3 are being studied as well as the effects of anti-PTH antisera on 1,25-(OH)2D3-induced resorption. c) Effects of various vitamin D metabolites on mineralization and collagen synthesis in vitro are being evaluated. Collaborative studies with several clinical investigators on 1,25-(OH)2D3 plasma concentrations in various pathophysiologic states will be continued. Further purification and characterization of a bone-resorbing substance from serum albumin is an additional ongoing project.